Integrated proteomic and transcriptomic analyses reveal unique protein composition of Th17 cell-derived extracellular traps in acne vulgaris.

Summary: Abstract Body: Extracellular traps (ETs), initially discovered in neutrophils, are now recognized in other immune cells, including T cells. Recent studies report antigen-specific T cells producing extracellular traps, but their protein composition and function remain poorly understood. This study aimed to investigate the protein composition of ETs produced by Th17 cells (TETs) and neutrophils (NETs) in response to different Cutibacterium acnes (C. acnes) phylotypes, to elucidate their roles in acne pathogenesis and identify potential therapeutic targets. We employed integrated proteomics, transcriptomics, and acne biopsy analyses to characterize their protein composition and gene profiles. Proteomic analysis revealed that while NETs exhibited consistent protein profiles across C. acnes phylotypes, TETs demonstrated significant compositional variation, indicating phylotype-specific immune responses. Unique TET-associated proteins, such as GZMM were implicated in bacterial cell wall disruption whereas T cell-associated molecules such as HLA-DRB5, and TAP1, were implicated in T-cell activation, and antigen presentation. Shared proteins between TETs and NETs, including H2BC21, HBD, and HMGN2, were associated with antimicrobial defense, bacterial entrapment, and anti-inflammatory regulation. Spatial transcriptomics further validated the distinct protein profiles of TETs within acne biopsies. These findings provide critical insights into the interplay between skin microbes and ET formation, offering a foundation for developing targeted acne treatments. Min Deng¹, Thao Tam To¹, Gregory M. Brewer¹, Matteo Pellegrini², George W. Agak¹ 1. University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA, United States. 2. University of California Los Angeles, Los Angeles, CA, United States. Innate Immunity, Microbiology, and Microbiome